The present invention relates to delivery methods, systems, and components thereof, for use with radiopharmaceutical materials, and especially with methods and components used for the determination of the specific activity or radiation concentration of a radiopharmaceutical material for delivery.
Radiopharmaceutical materials are well known in the medical field for both therapeutic as well as diagnostic purposes. Encapsulated radiopharmaceutical materials (as “seeds”) have been inserted into solid tumors such as prostate tumors to irradiate and thereby kill the tumor cells. Brief exposure of luminal cells in blood vessels to radioactive materials (held in place with a balloon catheter) after angioplasty has been used to reduce the incidence of restenosis in the blood vessel.
In addition to these therapeutic uses, radiopharmaceuticals can act as tracers in specific imaging techniques to help diagnose tissues requiring medical intervention. Two such imaging techniques are positron emission tomography (PET) and single photon emission computed tomography (SPECT). In PET imaging, a radiopharmaceutical that carries a positron emitting nuclide (such as 18F) is injected into a patient's vasculature. The positron emitted by the radionuclide collides with electrons in its vicinity, releasing a pair of gamma rays with opposing trajectories. The paired gamma rays are detected by sensors disposed on opposite sides of the patient, and the location of the radiopharmaceutical is thus determined. As an example, 18F-flourodeoxyglucose (FDG) is routinely used to detect tumor cells which preferentially take up the FDG. In SPECT imaging, the radiopharmaceutical carries a radionuclide that emits a single gamma ray photon during its disintegration. As with PET, the gamma ray is detected by sensors disposed about a patient and the location of the radiopharmaceutical is determined. As a non-limiting example, 99mTc sestamibi is administered into a patient's vasculature and monitored as the nuclide passes through the heart. This method provides a cardiologist with information regarding how well the heart is able to eject blood from the ventricles.
While the radiation dose from a diagnostic radiopharmaceutical is minimal for a single patient undergoing a single imaging procedure, the cumulative dose for either a medical technologist or physician who injects the tracer may be substantial. This is due to the number of patients the technologist or physician is required to inject on a daily basis. Consequently, a number of devices have been developed in order to help shield the physician or technologist from excess exposure to the radiopharmaceuticals. For manual injection of a radiopharmaceutical, syringes have been developed that incorporate shielding material in the body of the syringe (U.S. Pat. No. 4,968,305 to Takahashi et al.), and hand held shielded syringe holders have also been developed (U.S. Pat. No. 4,994,012 to Nakayama et al.). In addition to such manual devices, automated devices have also been described. Examples of such devices are found in U.S. Pat. No. 6,767,319 to Reilly et al. (herein incorporated by reference), PCT patent application publication WO 2004/004787 (Van Naemen et al., herein incorporated by reference), EPO patent application publication EP 1,616,587 (Buck, herein incorporated by reference), and U.S. patent application publication 2008/0177126 (Tate et al., herein incorporated by reference). While the application for these devices is primarily directed to PET imaging (and more specifically the use of FDG), similar style devices may be used for injecting SPECT radiopharmaceuticals for SPECT imaging procedures.
Referring to Buck and Tate et al. specifically, the automated injectors comprise in general the following components. A bulk source of a radiopharmaceutical such as a vial or other container is disposed within a shielded environment within the injector. A needle, cannula, or other access device is inserted into the container to allow access to the radiopharmaceutical material. A fluid pathway is further provided from the access device to a first pumping device which may include a syringe and activator, or peristaltic pump. A source of a nonradioactive flushing material such as saline is also provided with a second fluid path, which may be connected to a second pumping device, or may be in fluid communication with the first pumping device through a valve mechanism. In the example using a second pumping device, the output thereof may be in fluid communication with the output of the first pumping device via an auxiliary valve mechanism. The output end of the first pumping device is in fluid communication with a third fluid pathway which is disposed to pass through a radiation detector device such as an ion chamber. The third fluid pathway is connected to a second valve mechanism that controls the direction of the fluid therein to either a waste container, or to a delivery device which may deliver the radiopharmaceutical material to a receptacle or to a patient for medical purposes. A computer running appropriate software is able to control the actions of the first and second pumping devices via motor control devices, and in addition control the valve mechanisms. The injection device may also comprise a monitor to display information to a user (such as the amount of radiation detected by the radiation detector), as well as an input device to the computer (such as a keyboard) that permits the user to enter information regarding the operation of the injector.
From a functional perspective, such an automated device may be used in the following manner. A technologist or physician may load a bulk container or vial prefilled with a solution containing a radioactive material into a shielded receptacle in the injector. The amount of radioactive material such as specific activity (reported for example as Bq or Ci per unit volume) may be imprinted on a label of the prefilled vial. Alternatively, the total activity of the vial (as Bq or Ci) may be presented on a vial with a known or presumed volume of fluid. Once the prefilled vial or container is loaded into the shielded receptacle, an access device is inserted into the container either manually by the physician or technologist, or automatically by the injector. Similarly, a source of the non-radioactive flushing material, for example from a container or a hanging bag, is provided as well. The physician or technologist may then connect the flushing material to a second fluid pathway provided in the injector. The various fluid paths within the injector may be purged of air using the non-radioactive flushing material by means of a pumping process. The air purging process results in the fluid paths being filled with the flushing material, so no air is present for use. Thereafter, the physician or technologist activates the injector in a manner to provide a dose of the radiopharmaceutical for delivery. A variety of methods may be chosen to program the injector to deliver the amount of radiation required for delivery. For example, the physician or technologist user may enter a total delivery volume of radiopharmaceutical via the interface device on the injector. Alternatively, the user may enter the total radiation activity for a final dose. In such an example, the software in the injector computer would have information regarding the specific activity of the liquid in the radiopharmaceutical source and perform such calculations so as to determine the final volume to deliver. If a human patient is the recipient of the dose, parameters related to the patient (such as height and weight) may be input into the injector. In such an example, the software in the injector computer may use such information to determine the proper amount of radiopharmaceutical to deliver as an activity, and thereafter compute the total volume from the radiopharmaceutical source to deliver. These examples are not taken as exhaustive, and other methods may be used to program the injector to deliver a particular volume of the radiopharmaceutical for delivery.
Once the volume of radiopharmaceutical has been determined, the injector energizes the appropriate pumping mechanisms to transfer the required volume from the container sourcing the radiopharmaceutical into the third fluid path from the first pumping mechanism. A pumping method is then activated to pump the flushing fluid from the flushing fluid source into the third fluid pathway such that the bolus of the flushing fluid acts to push the dose of radiopharmaceutical along the fluid path. By this means, the dose of radiopharmaceutical progresses along the third fluid pathway until it enters into proximity of the radiation detector. As described in Tate et al., such a radiation detector may comprise an ion detector. Such an ion detector is briefly described as an enclosed container with a central anode and a collecting cathode between which an electrical potential is applied. The detector container is filled with a detecting gas (such as argon). When the radiation emitted by the radiopharmaceutical enters the ion detector, it ionizes some of the gas which results in positive and negative charges. The negative charges are attracted to the collecting anode, and a current is thereby created from the charged particles. The current produced by the radiation detector is then further processed by electronics and software to provide a reading of the number of disintegrations per second (as Bq or Ci) measured. As a result, the injector is provided direct information regarding the amount of radiation provided by the dose of radiopharmaceutical being delivered by the injector. As described in Buck, if the measured activity of the dose does not constitute a sufficient quantity of radiopharmaceutical, the injector can be programmed to provide a second dose, which in conjunction with the first, will provide the correct amount of radioactive pharmaceutical to be dispensed.
Once the correct volume of radiopharmaceutical is present in the third fluid path, the complete radiopharmaceutical dose is pumped out of the injector through a delivery device to its final destination. In the event that a dose has a radiation activity in excess of that required, valve mechanisms can be activated in the injector to dump the dose into a waste repository for removal.
As described in the above example of an automated radiopharmaceutical injector, the radiation concentration of the bulk pharmaceutical is presumed by the technologist or user to be correctly provided by labeling information on the bulk vial. This information must be entered into the injector system for dose calculations. It is not unusual for the concentration labeling information to be inaccurate to ±30%. Such inaccuracy may result in patient dosing levels below or greater than those desired. For this reason, it is desirable to include with the injector system, a system for directly measuring the specific activity or radiation concentration of the pharmaceutical as distributed in the bulk container.